Discovery proteomics studies for the identification of a protein panel associated with the response to pemetrexed in platinum drug resistant cancer

Pemetrexed is a drug largely used in lung cancer, mesothelioma and proposed in some cases of ovarian cancers, a particularly severe cancer type. In this latest tumor type, therapy relies on debulking surgery and platinum-based chemotherapy. Despite the initial high response rates to platinum drugs, most patients relapse and die from the disease. Considering the high levels of thymidylate synthase, dhydrofolate reductase and other folate related proteins in platinum drug resistant patients, pemetrexed was proposed as a second line drugs due to its known mechanism of action that engage the mentioned proteins. However a successful outcome could only be expected on the basis of patients’ stratifications. In the present study, a discovery proteomics approach was applied to tissue samples collected beforepemetrexed treatment from platinum resistant patients who relapsed after the first-line carboplatin-based chemotherapy but responded differently to the pemetrexed treatment.